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UniProtKB/Swiss-Prot Q9UQM7: Variant p.Thr286Pro

Calcium/calmodulin-dependent protein kinase type II subunit alpha
Gene: CAMK2A
Variant information

Variant position:  286
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Threonine (T) to Proline (P) at position 286 (T286P, p.Thr286Pro).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (T) to medium size and hydrophobic (P)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In MRD53; no effect on protein abundance; loss of autophosphorylation; loss of neuronal migration.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  286
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  478
The length of the canonical sequence.

Location on the sequence:   LKHPWISHRSTVASCMHRQE  T VDCLKKFNARRKLKGAILTT
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         LKHPWISHRSTVASCMHRQETVDCLKKFNARRKLKGAILTT

Mouse                         LKHPWISHRSTVASCMHRQETVDCLKKFNARRKLKGAILTT

Rat                           LKHPWISHRSTVASCMHRQETVDCLKKFNARRKLKGAILTT

Drosophila                    LKHPWICQRERVASVVHRQETVDCLKKFNARRKLKGAILTT

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 478 Calcium/calmodulin-dependent protein kinase type II subunit alpha
Modified residue 286 – 286 Phosphothreonine; by autocatalysis
Mutagenesis 286 – 286 T -> A. No effect on neuronal migration.
Mutagenesis 286 – 286 T -> D. Loss of neuronal migration.
Mutagenesis 286 – 286 T -> P. No effect on neuronal migration; when associated with R-42.
Helix 284 – 298


Literature citations

De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability.
Kuery S.; van Woerden G.M.; Besnard T.; Proietti Onori M.; Latypova X.; Towne M.C.; Cho M.T.; Prescott T.E.; Ploeg M.A.; Sanders S.; Stessman H.A.F.; Pujol A.; Distel B.; Robak L.A.; Bernstein J.A.; Denomme-Pichon A.S.; Lesca G.; Sellars E.A.; Berg J.; Carre W.; Busk O.L.; van Bon B.W.M.; Waugh J.L.; Deardorff M.; Hoganson G.E.; Bosanko K.B.; Johnson D.S.; Dabir T.; Holla O.L.; Sarkar A.; Tveten K.; de Bellescize J.; Braathen G.J.; Terhal P.A.; Grange D.K.; van Haeringen A.; Lam C.; Mirzaa G.; Burton J.; Bhoj E.J.; Douglas J.; Santani A.B.; Nesbitt A.I.; Helbig K.L.; Andrews M.V.; Begtrup A.; Tang S.; van Gassen K.L.I.; Juusola J.; Foss K.; Enns G.M.; Moog U.; Hinderhofer K.; Paramasivam N.; Lincoln S.; Kusako B.H.; Lindenbaum P.; Charpentier E.; Nowak C.B.; Cherot E.; Simonet T.; Ruivenkamp C.A.L.; Hahn S.; Brownstein C.A.; Xia F.; Schmitt S.; Deb W.; Bonneau D.; Nizon M.; Quinquis D.; Chelly J.; Rudolf G.; Sanlaville D.; Parent P.; Gilbert-Dussardier B.; Toutain A.; Sutton V.R.; Thies J.; Peart-Vissers L.E.L.M.; Boisseau P.; Vincent M.; Grabrucker A.M.; Dubourg C.; Tan W.H.; Verbeek N.E.; Granzow M.; Santen G.W.E.; Shendure J.; Isidor B.; Pasquier L.; Redon R.; Yang Y.; State M.W.; Kleefstra T.; Cogne B.; Petrovski S.; Retterer K.; Eichler E.E.; Rosenfeld J.A.; Agrawal P.B.; Bezieau S.; Odent S.; Elgersma Y.; Mercier S.;
Am. J. Hum. Genet. 101:768-788(2017)
Cited for: INVOLVEMENT IN MRD53; VARIANTS MRD53 SER-98; ASP-109; VAL-112; VAL-183; LEU-212; LEU-235; ARG-282 AND PRO-286; CHARACTERIZATION OF VARIANTS MRD53 ALA-98; ASP-109; ALA-138; VAL-183; LEU-212; LEU-235; ARG-282 AND PRO-286; FUNCTION; MUTAGENESIS OF THR-286;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.